THE CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) LOCUS AS A CANDIDATE GENE IN ABDOMINAL AORTIC-ANEURYSM

Abdominal aortic aneurysm (AAA) is a relatively common disease of the elderly presenting as progressive dilatation of the abdominal aorta. T he condition shows a pronounced tendency to cluster in families, indic ating a genetic component in the disease aetiology. We have screened t he cholesteryl ester transfer protein (CETP) gene, which has been prop osed as a candidate gene in AAA, by means of SSCP, DNA sequencing and restriction analysis in a cohort of patients with AAA and a matching c ontrol group drawn from the Irish population. The analysis has demonst rated sequence variation at four sites in the CETP gene: an A-T transv ersion in exon 9 (producing a Lys309-Stop codon substitution), a G-A t ransition in exon 14 (producing a conservative Val421-Ile substitution ), a C-T transition in intron 12 and a G-A transition in intron 15. No ne of the last three sites corresponded with sites of functional signi ficance in the protein, suggesting that this reflects neutral polymorp hism at the CETP locus. Furthermore, the frequencies of these four pol ymorphisms in the AAA patient and control groups were not significantl y different. These data therefore suggest that CETP may be excluded as a candidate gene in abdominal aortic aneurysm.